- Recent pre-clinical reports have begun to argue for the clinical testing of metronomic chemotherapy administration in various cancers. The theory of improved activity of Pazopanib + Topotecan administered metronomically is based on targeting tumor vasculature (both existing capillary endothelial cells and circulating bone marrow derived endothelial cell precursors), immune modulation, as well as tumor cell HIF-1 alpha inhibition, and the induction of DNA damage. Further support for the combination comes from recent data tying drug-induced VEGF inhibition to the induction of HIF-1 alpha activity in GBM suggesting possible synergy between Pazopanib and Topotecan